Some cancers and neoplasms are easier to treat with radiation than others. Hard-to-reach and and/or remove neoplasms, such as those in the esophagus, intestines and other lumens, are often treated via Brachytherapy. Brachytheraphy uses radioactive isotopes (commonly employed as seeds) to minimize radiation to adjacent, healthy tissue.
The radiation (dose distribution) depends on geometry especially the inverse square law, filtration by encapsulation material, and also adsorption in tissue and air. Individual seeds are shielded by the encapsulation process which usually limits the useful exposure to a short range of x- or gamma-rays. The initial dose rate would vary inversely with half-life. As an example, the typical initial dose rate for an Iodine 125 prostate implant would usually be about 0.07 Gy/hr (7 rad per hour as opposed to about 20 for Palladium 103. Host factors such as oxygenation, intrinsic radio sensitivity, proliferation rate, and repair capacity are more difficult to control.
Brachytherapy delivers radiation to small tissue volumes while limiting exposure of healthy tissue. In this regard, the delivered radiation conforms more to the target than any other form of radiation, (including proton therapy) as less normal transient tissue is treated. It features placement of radiation sources, such as small radioactive particles (usually as encapsulated seeds directly or in tubes or needles) near or within the target tissue, thus having the advantage over External Beam Radiation Therapy (EBRT) of being more focalized and less damaging to surrounding healthy tissue.
Brachytherapy is a common treatment for esophageal, prostate, and other cancers. Approximately 15,000 and 480,000 cases of esophageal cancer are diagnosed in the U.S. and worldwide, respectively. At least 50 percent of patients fail locally who present with curable cancers, which is to say that 50 percent suffer from persistence or recurrence of the cancers at the original cancer site. (Esophageal cancer treatment is a reasonable prototype for luminal brachytherapy that could be expanded to other sites.)
Brachytherapy can be delivered in several rates: a Low-Dose Rate (LDR, or less than 2 Gy/hr), a High-Dose Rate (HDR or greater than 12 Gy/hr), and a very Low Dose Rate vLDR. There is a Medium Dose Rate or hybrid at 2-12 gy/hr. The rates are expressed in Grays (Gy)/hour which are SI units of energy absorbed from ionizing radiation, equal to the absorption of one joule of radiation energy by one kilogram of matter. Since the inception of brachytherapy at the beginning of the 20th century (i.e., soon after the discovery of radiation) delivery has been predominately LDR.
LDR brachytherapy typically delivers radiation at a rate of about 40 to 50 cGy/hr (e.g., 0.4 Gy/hr) while HDR typically delivers at a rate of about 0.2 Gy/minute. The instantaneous rate is much higher at each dwell location for HDR brachytherapy as the very active source must traverse the various treatment locations during each treatment.
LDR brachytherapy delivers radiation continuously (as prescribed relatively uniformly throughout the implanted volume), while HDR brachytherapy delivers radiation intermittently over several days. Regardless of the dose rate, a total final dosage of 60 Gy or less is usually delivered to the patient during LDR brachytherapy if it is the sole source of radiotherapy, and a total dose of 20-40 Gy is delivered during brachytherapy when used in combination with other forms of radiation treatment. These scenarios involve temporary implants in which the device is removed after completion of treatment. Very low dose radiation (vLDR) applicators can be used as LDR sources.
Brachytherapy has been used for more than half a century to treat prostate cancer. In this situation, low activity material emitting a low energy is placed next to or within a tumor. Until now these low emitting devices have mostly been left in place permanently except in extraordinary circumstances. The most commonly employed vLDR source (also known as permanent seeds) is Iodine-125 (125I). 125I decays at a low energy radiation of 30 keV and emits radiation at a dose rate of about 0.04-0.1 Gy/hr (4 to 10 cGy/hr) continuously, up to a nominal year. vLDR is commonly used for cancers in which the radiation source can be placed proximate to or in the neoplasm and left for a significant period of time or permanently, such as when radioactive material or seeds are placed in prostate tumors.
Clinicians administer HDR brachytherapy in multiple sessions to improve patient tolerance. Thus, the patient is subjected to the additional risk of multiple procedures, often requiring anesthesia. Patients with cancers within lumen, ducts, or tracts, such as cancer of the esophagus or biliary tract of the liver, have less tolerance for brachytherapy if connections (for example, catheters) are connected externally for multiple days. Such protracted use of catheters often leads to kinking, dislodgement, obstruction, irritation, and the risk of life-threatening infections. (The most commonly employed HDR radio isotopic source is Ir 192 with an energy of 0.38 MEV and half live of 74 days. Cs 137 (T1/2 30.2 years energy 0.662 MEV and Co 60 T1/2 5 years and energy of 1.2 MEV have occasionally been used.)
HDR employs a primary housing containing a relatively high energy source (about 10 Ci), often as Iridium-192 (0.4 MeV). Treatment sessions last about 30 minutes. HDR is commonly applied in 2 to 3 daily sessions over the course of a few days, or multiple placement of an after-loading catheter in e.g. esophageal cancer treatment with multiple procedures and anesthesia.
Brachytherapy dosage is usually calculated at a fixed distance (or as a volume measuring the MPD or minimal peripheral dose) from the radiation source. HDR requires a highly active source delivering radiation at a dose rate of about 12 to 20 Gy/hr. Hot and cold spots, due to uneven distribution of radiation dose, occur with small deviations in distance between the tissue and the radiation source. Thus, brachytherapy treatment using a centralized radioactive material housing or containment can result in significant patient toxicity if the radioactive source is too close to normal or target tissues. For example, for patients with esophagus cancer, potentially life-threatening fistulas and hemorrhages occurred at a rate of 12 percent when treated with HDR brachytherapy in the study of Gasper et al, International Journal of Radiation Oncology, Biology, Physics 38 (1) 127-321 (1997). However, there are many reasons for the source to be skewed to one side as even an active tumor could displace the source. Lastly, HDR treatment requires a specially shielded patient room with appropriate radiation precautions. The vLDR applications disclosed in the instant specification do not.
State of the art devices for delivering radiation to internal tissues lack two important essential features: 1) the ability to remove or replace the radiation sources in situ when clinically appropriate, and 2) the ability to change the geometry, energy or radioactive sources of the radioactive particles or seeds in situ according to clinical needs. Typically, once the radiation source carrier(s) and the radiation source(s) is/are placed, they remain permanently within the patient or for the duration of patient treatment. Leaving a permanent radiation source in a patient, where it or its carrier may migrate over time or the tumor may change in shape or size, has the potential undesirable effect that healthy tissue will be exposed to the excessive radiation, while the target cancerous tissue is not. The ability to remove the radioactive sources in this situation or prior to surgery, while clinically useful, is currently lacking from the state of the art, as is the ability to easily localize the brachytherapy treatment or stent in vivo in the doctor's office without requiring formal imaging. In the event of a patient's death, it also may be desirable to remove the sources before cremation or burial.
Additionally, it may be clinically necessary to continue radiation therapy after the activity of the radioactive material has decayed. For example, 125I has a half-life of about 60 days. If the tumor is still present or grows in size after an initial brachytherapy treatment (which sometimes occurs within six months), then it would be advantageous to replace the depleted radiation source with a source that has higher activity, a shorter half-life, that covers a longer length treatment site, or is marginally located. This is because new, perhaps faster growing, tumors may be better controlled with radiation that has a shorter half-life or that decays and emits radiation faster. Surviving tumor clones may have different biology and require faster or even slower radiation exposure rates for sterilization.
Approximately ninety percent of tumor recurrences occur where the original tumor was abutting healthy tissue. However, state of the art methods for delivering radiation at these margin areas after tumor excision have drawbacks. For example, radioactive seed-carrying sutures are sometimes used with absorbable mesh to close up excision sites. But the suture positions shift in time and the mesh may be absorbed by the body. This often leads to the sutures sometimes collapsing on themselves, and otherwise not maintaining the optimal seed positioning relative to the neoplasm or vulnerable tissue. Under-dosing occurs, which can lead to recurrence. Conversely, over dosing occurs, leading to injury to healthy tissue.
It would be advantageous to adjust the position and the activity of the radioactive source on its carrier in response to changes in tumor shape and size, carrier position, and other relevant therapeutic factors. It also may be appropriate to remove the radiation sources before surgery or other intervention to reduce personnel exposure or damage/contamination to sensitive equipment. Finally, it may be clinically useful to load the radioactive sources sometime after the placement of the device. None of the state of the art addresses provides these features.
Therefore, a need exists in the art for a method and device to deliver radiation and other medicaments to a patient while maintaining the original shape and size of the pre-operative surgical site (e.g., post lumpectomy). The device could be made to mimic the natural feel and bulk of original tissue simultaneous with delivering low level or high level radiation doses. The device should allow for embedment of radioactive particles in a reversibly deformable carrier and post-surgical repositioning of the carrier.